• Je něco špatně v tomto záznamu ?

Anti-Lymphoma Efficacy Comparison of Anti-Cd20 Monoclonal Antibody-Targeted and Non-Targeted Star-Shaped Polymer-Prodrug Conjugates

O. Lidický, O. Janoušková, J. Strohalm, M. Alam, P. Klener, T. Etrych,

. 2015 ; 20 (11) : 19849-64. [pub] 20151104

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc16027975

Here we describe the synthesis and biological properties of two types of star-shaped polymer-doxorubicin conjugates: non-targeted conjugate prepared as long-circulating high-molecular-weight (HMW) polymer prodrugs with a dendrimer core and a targeted conjugate with the anti-CD20 monoclonal antibody (mAb) rituximab (RTX). The copolymers were linked to the dendrimer core or to the reduced mAb via one-point attachment forming a star-shaped structure with a central antibody or dendrimer surrounded by hydrophilic polymer chains. The anticancer drug doxorubicin (DOX) was attached to the N-(2-hydroxypropyl)methacrylamide (HPMA)-based copolymer chain in star polymer systems via a pH-labile hydrazone linkage. Such polymer-DOX conjugates were fairly stable in aqueous solutions at pH 7.4, and the drug was readily released in mildly acidic environments at pH 5-5.5 by hydrolysis of the hydrazone bonds. The cytotoxicity of the polymer conjugates was tested on several CD20-positive or negative human cell lines. Similar levels of in vitro cytotoxicity were observed for all tested polymer conjugates regardless of type or structure. In vivo experiments using primary cell-based murine xenograft models of human diffuse large B-cell lymphoma confirmed the superior anti-lymphoma efficacy of the polymer-bound DOX conjugate when compared with the original drug. Targeting with RTX did not further enhance the anti-lymphoma efficacy relative to the non-targeted star polymer conjugate. Two mechanisms could play roles in these findings: changes in the binding ability to the CD-20 receptor and a significant loss of the immunological properties of RTX in the polymer conjugates.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc16027975
003      
CZ-PrNML
005      
20161027102053.0
007      
ta
008      
161005s2015 sz f 000 0|eng||
009      
AR
024    7_
$a 10.3390/molecules201119664 $2 doi
024    7_
$a 10.3390/molecules201119664 $2 doi
035    __
$a (PubMed)26556320
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a sz
100    1_
$a Lidický, Ondřej $u Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovský Sq. 2, 162 06 Prague 6, Czech Republic. lidicky@imc.cas.cz.
245    10
$a Anti-Lymphoma Efficacy Comparison of Anti-Cd20 Monoclonal Antibody-Targeted and Non-Targeted Star-Shaped Polymer-Prodrug Conjugates / $c O. Lidický, O. Janoušková, J. Strohalm, M. Alam, P. Klener, T. Etrych,
520    9_
$a Here we describe the synthesis and biological properties of two types of star-shaped polymer-doxorubicin conjugates: non-targeted conjugate prepared as long-circulating high-molecular-weight (HMW) polymer prodrugs with a dendrimer core and a targeted conjugate with the anti-CD20 monoclonal antibody (mAb) rituximab (RTX). The copolymers were linked to the dendrimer core or to the reduced mAb via one-point attachment forming a star-shaped structure with a central antibody or dendrimer surrounded by hydrophilic polymer chains. The anticancer drug doxorubicin (DOX) was attached to the N-(2-hydroxypropyl)methacrylamide (HPMA)-based copolymer chain in star polymer systems via a pH-labile hydrazone linkage. Such polymer-DOX conjugates were fairly stable in aqueous solutions at pH 7.4, and the drug was readily released in mildly acidic environments at pH 5-5.5 by hydrolysis of the hydrazone bonds. The cytotoxicity of the polymer conjugates was tested on several CD20-positive or negative human cell lines. Similar levels of in vitro cytotoxicity were observed for all tested polymer conjugates regardless of type or structure. In vivo experiments using primary cell-based murine xenograft models of human diffuse large B-cell lymphoma confirmed the superior anti-lymphoma efficacy of the polymer-bound DOX conjugate when compared with the original drug. Targeting with RTX did not further enhance the anti-lymphoma efficacy relative to the non-targeted star polymer conjugate. Two mechanisms could play roles in these findings: changes in the binding ability to the CD-20 receptor and a significant loss of the immunological properties of RTX in the polymer conjugates.
650    _2
$a zvířata $7 D000818
650    _2
$a protinádorové látky $x chemie $x farmakologie $7 D000970
650    _2
$a apoptóza $x účinky léků $7 D017209
650    _2
$a nádorové buněčné linie $7 D045744
650    _2
$a viabilita buněk $x účinky léků $7 D002470
650    _2
$a modely nemocí na zvířatech $7 D004195
650    _2
$a doxorubicin $x chemie $x farmakologie $7 D004317
650    _2
$a lékové transportní systémy $7 D016503
650    _2
$a uvolňování léčiv $7 D065546
650    _2
$a lidé $7 D006801
650    _2
$a lymfom $x farmakoterapie $x mortalita $x patologie $7 D008223
650    _2
$a myši $7 D051379
650    12
$a polymery $x chemie $7 D011108
650    12
$a prekurzory léčiv $x chemie $x farmakologie $7 D011355
650    _2
$a rituximab $x chemie $x farmakologie $7 D000069283
650    _2
$a xenogenní modely - testy protinádorové aktivity $7 D023041
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Janoušková, Olga $u Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovský Sq. 2, 162 06 Prague 6, Czech Republic. janouskova@imc.cas.cz.
700    1_
$a Strohalm, Jiří $u Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovský Sq. 2, 162 06 Prague 6, Czech Republic. strohalm@imc.cas.cz.
700    1_
$a Alam, Mahmudul $u Institute of Pathological Physiology, First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 128 53 Prague 2, Czech Republic. mahmuddso2004@gmail.com. $7 gn_A_00003252
700    1_
$a Klener, Pavel $u Institute of Pathological Physiology, First Faculty of Medicine, Charles University in Prague, U Nemocnice 5, 128 53 Prague 2, Czech Republic. pavel.klener@gmail.com. Department of Hematology, Charles University General Hospital in Prague, U Nemocnice 2, 128 08 Prague 2, Czech Republic. pavel.klener@gmail.com.
700    1_
$a Etrych, Tomáš $u Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Heyrovský Sq. 2, 162 06 Prague 6, Czech Republic. etrych@imc.cas.cz.
773    0_
$w MED00180394 $t Molecules (Basel, Switzerland) $x 1420-3049 $g Roč. 20, č. 11 (2015), s. 19849-64
856    41
$u https://pubmed.ncbi.nlm.nih.gov/26556320 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20161005 $b ABA008
991    __
$a 20161027102510 $b ABA008
999    __
$a ok $b bmc $g 1166289 $s 952605
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2015 $b 20 $c 11 $d 19849-64 $e 20151104 $i 1420-3049 $m Molecules $n Molecules $x MED00180394
LZP    __
$a Pubmed-20161005
Zpět

Najít záznam

Citační ukazatele

    Možnosti archivace